Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, C117

Oral Communications

Anticonvulsant effects of GWP42006 in vitro and in vivo in rat

A. J. Hill1,2, N. A. Jones1,2, G. J. Stephens1, C. M. Williams2, B. J. Whalley1

1. Reading School of Pharmacy, University of Reading, Reading, Berkshire, United Kingdom. 2. School of Psychology & Clinical Language Sciences, University of Reading, Reading, Berkshire, United Kingdom.

  • Effects of GWP42006 in dentate gyrus (DG), CA3 and CA1 hippocampal regions, data is mean % of control ±S.E.M; * = p≤0.05 and ** = p≤ 0.01, Wilcoxon paired test. n=9-13 electrodes.

Epilepsy is a chronic CNS disorder characterised by recurrent seizures; a third of cases are pharmacologically intractable. We have previously shown that two phytocannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabivarin, possess anticonvulsant potential (1, 2). Here, we extend our investigations to phytocannabinoid GWP42006, using two in vitro epileptiform models in rat hippocampal brain slices and the in vivo pentylenetetrazole (PTZ) model of generalised seizures in rat. The activity of acute hippocampal slices from P>21 Wistar rats was recorded by multi-electrode arrays (MEA)(3). To induce epileptiform activity, either Mg2+o was removed (Mg2+o-free model) or 100μM 4-aminopyridine added (4-AP model). 30 min after epileptiform burst activity was established, GWP42006 was added cumulatively (1, 10, 100μM; 30 min each). The effects of GWP42006 on epileptiform burst amplitude and duration were measured (see Table). Overall, GWP42006 at ≥10μM significantly decreased burst duration and amplitude in both models, CA3 was least sensitive to the anti-epileptiform effects of GWP42006. For in vivo studies, GWP42006 (50, 100 or 200mg kg-1) or vehicle was administered I.P. (n=15 P>21 Wistar rats/group). 60 min later, animals received 80mg kg-1 PTZ I.P. and were video recorded for later analysis of seizures (1). The median seizure severity of the 200mg kg-1 GWP42006 group was significantly lower than the vehicle group (clonic vs. tonic-clonic, ANOVA p<0.05). Mortality was significantly lower after 100 and 200mg kg-1 GWP42006 treatment than vehicle (13, 7 and 53% respectively; binomial test p<0.05). Finally, the proportion of seizure-free animals was significantly higher after 200mg kg-1 GWP42006 than vehicle (33 and 7% respectively; binomial test p<0.05). These data demonstrate the anticonvulsant properties of GWP42006 and suggest it may hold clinical potential as an epilepsy treatment.

Where applicable, experiments conform with Society ethical requirements